The second series of flexible shape-modified nucleosides is introduced. The “fleximers” feature thepurine ring systems split into their individual imidazole and pyrimidine components. This structuralmodification serves to introduce flexibility to the nucleoside while still retaining the elementsessential for recognition. As a consequence, these structurally innovative nucleosides can morereadily adapt to their environment and should find use as bioprobes for investigating enzyme−coenzyme binding sites as well as nucleic acid and protein interactions. Their design and synthesisis described.